P15 VALIDATION OF THE NOVEL EUROPEAN MYELOMA NETWORK PROGNOSTIC SCORE (R2-ISS) IN AN INDEPENDENT REAL-WORLD SETTING
Authors: G Cengiz Seval, M Aydoğan, MH Akbulut, B Karakaya, G Yavuz, H Yilmaz, M Beksac
Journal: HemaSphere (2023)

INTRODUCTION: Since the introduction of ISS, there has been a major advance in the field of prognostic biomarkers that led to a revision (R-ISS) which was still beyond expectations. 1q gain (+1q) is a high risk cytogenetic (HCR) feature among newly diagnosed multiple myeloma (NDMM). +1q has recently been integrated into the Second Revision of the ISS (R2-ISS) by the European Myeloma Network (EMN) under the umbrella of the European Union-funded HARMONY project. In this retrospective analysis, we aimed to validate this novel score and evaluate its impact on the outcome of NDMM. METHODS: This retrospective study is performed on a database of 524 consecutive NDMM patients treated in our center between September 2007- March 2022. As 1q amplification has been added to our FISH panels lately, 208 consecutive patients met the criteria for R2-ISS score parameters. Progression eligible for analysis-free survival (PFS) was defined as the time from the diagnosis until disease progression, relapse, or death due to any cause. Overall survival (OS) was defined as the time from the diagnosis until death due to any cause or last follow-up. Analysis was performed by SPSS software version 26.0 (SPSS, Inc., IBM, Armonk, NY). RESULTS: Patients (median age 62 years (33-88 years); (44.1% female and 55.9% male)) received either bortezomib-based triplet (90%) without (n: 405) or with an immunomodulatory drug (IMID) (13.2%) as induction therapy. Out of the total, 493 patients underwent autologous hematopoietic stem cell transplantation (AHCT). As a post-ASCT treatment, consolidation (20.2%) and maintenance (46.4%) were given to 243 patients. The median follow-up for all patients is 35.4 months (range: 3-237 mos). HCR was detected in 90 patients (17.8%) among all patients and +1q was identified in 96 cases, accounting for 46.2% of 208 patients. Based on the calculation of risk score in R2-ISS; 21 patients (10.1%) ranked as score 0 (R2-ISS I; low), 50 patients (24%) score 0.5-1 (R2-ISS II; low-intermediate), 111 patients (53.4%) score 1.5-2.5 (R2-ISS III; intermediate-high) and 26 patients (12.5%) score 3-5 (R2-ISS IV; high). The cross-tabulation of R2-ISS with R-ISS is shown in Table 1. With a median follow-up of 33.8 months, patients with +1q had significantly shorter PFS (95% CI: 20.4%-47.1%, p<0.001) than those without +1q. The median PFS was NR vs NR vs 55.3 mos vs 19.7 mos, with 5-year OS of NR vs 95.4% vs 85.3% vs 66.2% in the R2-ISS I, II, III, and IV groups, respectively (p<0.001 and p=0.002). Three-year PFS and OS are statistically significant for ISS, R-ISS, and R2-ISS groups (Figure 1). CONCLUSION: Our single-center uniform real World data-based study confirms the prognostic role of the new R2-ISS scoring system as a reliable and reproducible method to powerfully predict the prognosis of patients with NDMM. Based on the results of this study, the presence of +1q confers poor outcomes that provide robust proof for the revision of +1q in the R2-ISS. Furthermore, R2-ISS is able to characterize very good prognostic and ultra-high-risk patients not possible in the earlier R-ISS and ISS models. Acknowledgment: We are indebted to Ankara University School of Medicine Department of Medical Genetics FISH laboratory staff members and especially Asist. Prof. Timur Tuncali performed the FISH analysis of the patients.